Low Dose Treosulfan Based Conditioning Regimen in HSCT for Nijmegen Breakage Syndrome

Nijmegen Breakage Syndrome Clinical Trial

Official title:

Clinical Open-label Phase 2 Study of Low Dose Treosulfan Based Conditioning Regimen Efficacy in Hematopoietic Stem Cell Transplantation for Children With Nijmegen Breakage Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04400045
• Other study ID #: NCPHOI-2020-04
• Status: Recruiting
• Phase: Phase 2
• Start date: May 22, 2020
• Est. completion date: May 2023

Study information

• Verified date: June 2020
• Source: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Contact: Dmitry Balashov, MD, PhD
• Phone: +74952876570
• Email: bala8[@]yandex.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the current study is to evaluate the safety and efficacy of low dose treosulfan based conditioning regimen in HSCT in Nijmegen breakage syndrome

Description:

Nijmegen breakage syndrome (NBS) is a DNA repair disorder. The only curative option for combine immunodeficiency in NBS is allogeneic hematopoietic stem cell transplantation (HSCT). Standard myeloablative conditioning regimens in DNA repair disorders lead to increased morbidity and mortality after HSCT. Low doses of alkylators are used to reduce toxicity rates, which, however, increase the risks of mixed chimerism and graft failure. The data of treosulfan usage in NBS are sparse. To evaluate the safety and efficacy of low dose treosulfan based conditioning regimen in NBS, treosulfan 21g/m2 in combination with fludarabine 150mg/mg, cyclophosphamide 40mg/kg, thymoglobulin (Genzyme) 5mg/kg and rituximab 100mg/m2 will be used from day -6 to -1 day, followed by stem cell infusion. The primary endpoint is event-free survival, where graft failure, death, and malignancies are considered as events.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: May 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 21 Years

Eligibility

Inclusion Criteria:

1. Patients aged = 3 months and < 21 years

2. Patients diagnosed with NBS eligible for an allogeneic HSCT

3. Signed written informed consent signed by a parent or legal guardian

Related Conditions & MeSH terms

• Nijmegen Breakage Syndrome
• Syndrome

Intervention

Drug:
• Treosulfan
Treosulfan 21mg/m2 (days -6, -5, -4)

Locations

Country	Name	City	State
Russian Federation	HSCT department	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival	Events: graft failure, death, malignancies	3 years after HSCT
Secondary	Overall survival		3 years after HSCT
Secondary	Cumulative incidence of engraftment		100 days
Secondary	Cumulative incidence of graft failure		3 years
Secondary	Cumulative incidence of viral infections		1 year
Secondary	Cumulative incidence of acute graft versus host disease		1 year
Secondary	Cumulative incidence of chronic graft versus host disease		3 years
Secondary	Incidence of early organ toxicity		100 days
Secondary	Cumulative incidence of transplant related mortality		3 years
Secondary	Incidence of long-term toxicity	malignancies, non-malignant complications	3 years